Cerebral Hemispheres 2

NEUROSCIENTIFICALLY CHALLENGED

NEUROSCIENCE MADE SIMPLER

The Chicken and the Egg of Alzheimer’s

February 8, 2008


Alzheimer’s disease (AD) is the most common form of elderly dementia, affecting over 25 million people worldwide. Some estimates put new cases of AD at 4-5 million per year (one new case every 7 seconds). The neurodegenerative effects of AD are devastating, causing cognitive deterioration that can lead to invalidism and drastic memory loss. Furthermore, AD is a frustrating disease to scientists and doctors because, although there are signature neurological changes that accompany its progression, the etiology remains unknown.

Two of the hallmark signs of AD—and putative culprits for its causation—are amyloid plaques and microglia. Amyloid plaques, also known as senile plaques, are buildups of fibrous protein material known as amyloid. They are not specific to AD, and can be seen in the brains of older people in general. They are much more prevalent in an AD-afflicted brain, however, and are associated with neurodegeneration. Microglia, on the other hand, are part of the immune system of the brain. Their job is to detect foreign agents in the brain and quickly eradicate them. The substances microglia secrete to protect neurons, however, can also be neurotoxic in excess.

There has been an ongoing debate among scientists as to what comes first in AD, the plaques or the microglia? Some have argued that overactivity of microglia causes the plaques to appear, leading to AD. Others have asserted the opposite, that the plaques develop, causing microglia to accumulate as an immune response. This in time becomes neurotoxic due to continued development of plaques.

A group of researchers from Harvard Medical School believe they have answered the question at the heart of this debate. The group experimented with mice that were genetically engineered to develop amyloid plaques. They surgically placed a small window in the skulls of the mice so they could check for plaque formation daily. They found that amyloid plaques formed independently, which instigated an immune response by microglia. The microglia actually seemed to limit the growth of the plaques, but cognitive degeneration still progressed. The researchers suggested this was because amyloid fragments were being broken off of the plaques and damaging surrounding neurons.

Another important finding from the study was that the plaques formed much more quickly than previously thought possible—sometimes in only one day. Cognitive impairment consistent with AD followed several days afterward. This came as a surprise, as it was believed plaque formation should take weeks, or months, to occur. While the researchers are quick to note this was an experiment with mice and may not be directly applicable to humans, they also point out this may underscore the importance of developing prophylactic treatments for plaques in order to defeat AD. There are currently drugs in clinical trials that are designed to do just that, by inhibiting an enzyme integral to amyloid development. The results of the phase III trials of one such drug should be released this summer.

YOUR BRAIN, EXPLAINED

Sleep. Memory. Pleasure. Fear. Language. We experience these things every day, but how do our brains create them? Your Brain, Explained is a personal tour around your gray matter. Building on neuroscientist Marc Dingman’s popular YouTube series, 2-Minute Neuroscience, this is a friendly, engaging introduction to the human brain and its quirks using real-life examples and Dingman’s own, hand-drawn illustrations.

  • Reading like a collection of detective stories, Your Brain, Explained combines classic cases in the history of neurology with findings stemming from the latest techniques used to probe the brain’s secrets. - Stanley Finger, PhD, Professor Emeritus of Psychological & Brain Sciences, Washington University (St. Louis), author, Origins of Neuroscience

  • ...a highly readable and accessible introduction to the operation of the brain and current issues in neuroscience... a wonderful introduction to the field. - Frank Amthor, PhD, Professor of Psychology, The University of Alabama at Birmingham, author, Neuroscience for Dummies

  • Dingman weaves classic studies with modern research into easily digestible sections, to provide an excellent primer on the rapidly advancing field of neuroscience. - Moheb Costandi, author, Neuroplasticity and 50 Human Brain Ideas You Really Need to Know

  • An informative, accessible and engaging book for anyone who has even the slightest interest in how the brain works, but doesn’t know where to begin. - Dean Burnett, PhD, author, Happy Brain and Idiot Brain